<!doctype html>
<html>
<head>
<!-- Global site tag (gtag.js) - Google Analytics -->
<script async src="https://www.googletagmanager.com/gtag/js?id=UA-114672259-1"></script>
<script>
  window.dataLayer = window.dataLayer || [];
  function gtag(){dataLayer.push(arguments);}
  gtag('js', new Date());
  gtag('config', 'UA-114672259-1');
  gtag('set', {'user_id': 'USER_ID'});
</script>
<meta charset='UTF-8'><meta name='viewport' content='width=device-width initial-scale=1'>
<title>15SMRT测序在靶向捕获方面的更多应用.md</title><link href='http://fonts.googleapis.com/css?family=Open+Sans:400italic,700italic,700,400&subset=latin,latin-ext' rel='stylesheet' type='text/css'><style type='text/css'>html, body {overflow-x: initial !important;}html { font-size: 14px; background-color: rgb(255, 255, 255); color: rgb(51, 51, 51); }
body { margin: 0px; padding: 0px; height: auto; bottom: 0px; top: 0px; left: 0px; right: 0px; font-family: 'Helvetica Neue', Helvetica, Arial, sans-serif; font-size: 1rem; line-height: 1.42857143; overflow-x: hidden; background-image: inherit; background-size: inherit; background-attachment: inherit; background-origin: inherit; background-clip: inherit; background-color: inherit; background-position: inherit inherit; background-repeat: inherit inherit; }
a:active, a:hover { outline: 0px; }
.in-text-selection, ::selection { background-color: rgb(181, 214, 252); text-shadow: none; background-position: initial initial; background-repeat: initial initial; }
#write { margin: 0px auto; height: auto; width: inherit; word-break: normal; word-wrap: break-word; position: relative; padding-bottom: 70px; white-space: pre-wrap; overflow-x: auto; }
.for-image #write { padding-left: 8px; padding-right: 8px; }
body.typora-export { padding-left: 30px; padding-right: 30px; }
@media screen and (max-width: 500px) { 
  body.typora-export { padding-left: 0px; padding-right: 0px; }
  .CodeMirror-sizer { margin-left: 0px !important; }
  .CodeMirror-gutters { display: none !important; }
}
.typora-export #write { margin: 0px auto; }
#write > p:first-child, #write > ul:first-child, #write > ol:first-child, #write > pre:first-child, #write > blockquote:first-child, #write > div:first-child, #write > table:first-child { margin-top: 30px; }
#write li > table:first-child { margin-top: -20px; }
img { max-width: 100%; vertical-align: middle; }
input, button, select, textarea { color: inherit; font-family: inherit; font-size: inherit; font-style: inherit; font-variant-caps: inherit; font-weight: inherit; line-height: inherit; }
input[type="checkbox"], input[type="radio"] { line-height: normal; padding: 0px; }
::before, ::after, * { box-sizing: border-box; }
#write p, #write h1, #write h2, #write h3, #write h4, #write h5, #write h6, #write div, #write pre { width: inherit; }
#write p, #write h1, #write h2, #write h3, #write h4, #write h5, #write h6 { position: relative; }
h1 { font-size: 2rem; }
h2 { font-size: 1.8rem; }
h3 { font-size: 1.6rem; }
h4 { font-size: 1.4rem; }
h5 { font-size: 1.2rem; }
h6 { font-size: 1rem; }
p { -webkit-margin-before: 1rem; -webkit-margin-after: 1rem; -webkit-margin-start: 0px; -webkit-margin-end: 0px; }
.mathjax-block { margin-top: 0px; margin-bottom: 0px; -webkit-margin-before: 0rem; -webkit-margin-after: 0rem; }
.hidden { display: none; }
.md-blockmeta { color: rgb(204, 204, 204); font-weight: bold; font-style: italic; }
a { cursor: pointer; }
#write input[type="checkbox"] { cursor: pointer; width: inherit; height: inherit; margin: 4px 0px 0px; }
tr { break-inside: avoid; break-after: auto; }
thead { display: table-header-group; }
table { border-collapse: collapse; border-spacing: 0px; width: 100%; overflow: auto; break-inside: auto; text-align: left; }
table.md-table td { min-width: 80px; }
.CodeMirror-gutters { border-right-width: 0px; background-color: inherit; }
.CodeMirror { text-align: left; }
.CodeMirror-placeholder { opacity: 0.3; }
.CodeMirror pre { padding: 0px 4px; }
.CodeMirror-lines { padding: 0px; }
div.hr:focus { cursor: none; }
pre { white-space: pre-wrap; }
.CodeMirror-gutters { margin-right: 4px; }
.md-fences { font-size: 0.9rem; display: block; break-inside: avoid; text-align: left; overflow: visible; white-space: pre; background-image: inherit; background-size: inherit; background-attachment: inherit; background-origin: inherit; background-clip: inherit; background-color: inherit; position: relative !important; background-position: inherit inherit; background-repeat: inherit inherit; }
.md-diagram-panel { width: 100%; margin-top: 10px; text-align: center; padding-top: 0px; padding-bottom: 8px; overflow-x: auto; }
.md-fences .CodeMirror.CodeMirror-wrap { top: -1.6em; margin-bottom: -1.6em; }
.md-fences.mock-cm { white-space: pre-wrap; }
.show-fences-line-number .md-fences { padding-left: 0px; }
.show-fences-line-number .md-fences.mock-cm { padding-left: 40px; }
.footnotes { opacity: 0.8; font-size: 0.9rem; padding-top: 1em; padding-bottom: 1em; }
.footnotes + .footnotes { margin-top: -1em; }
.md-reset { margin: 0px; padding: 0px; border: 0px; outline: 0px; vertical-align: top; background-color: transparent; text-decoration: none; text-shadow: none; float: none; position: static; width: auto; height: auto; white-space: nowrap; cursor: inherit; line-height: normal; font-weight: normal; text-align: left; box-sizing: content-box; direction: ltr; background-position: initial initial; background-repeat: initial initial; }
li div { padding-top: 0px; }
blockquote { margin: 1rem 0px; }
li p, li .mathjax-block { margin: 0.5rem 0px; }
li { margin: 0px; position: relative; }
blockquote > :last-child { margin-bottom: 0px; }
blockquote > :first-child { margin-top: 0px; }
.footnotes-area { color: rgb(136, 136, 136); margin-top: 0.714rem; padding-bottom: 0.143rem; }
@media print { 
  html, body { height: 100%; }
  .typora-export * { -webkit-print-color-adjust: exact; }
  h1, h2, h3, h4, h5, h6 { break-after: avoid-page; orphans: 2; }
  p { orphans: 4; }
  html.blink-to-pdf { font-size: 13px; }
  .typora-export #write { padding-left: 1cm; padding-right: 1cm; }
  .typora-export #write::after { height: 0px; }
  @page { margin: 20mm 0mm; }
}
.footnote-line { margin-top: 0.714em; font-size: 0.7em; }
a img, img a { cursor: pointer; }
pre.md-meta-block { font-size: 0.8rem; min-height: 2.86rem; white-space: pre-wrap; background-color: rgb(204, 204, 204); display: block; overflow-x: hidden; background-position: initial initial; background-repeat: initial initial; }
p .md-image:only-child { display: inline-block; width: 100%; text-align: center; }
#write .MathJax_Display { margin: 0.8em 0px 0px; }
.mathjax-block { white-space: pre; overflow: hidden; width: 100%; }
p + .mathjax-block { margin-top: -1.143rem; }
.mathjax-block:not(:empty)::after { display: none; }
[contenteditable="true"]:active, [contenteditable="true"]:focus { outline: none; box-shadow: none; }
.task-list { list-style-type: none; }
.task-list-item { position: relative; padding-left: 1em; }
.task-list-item input { position: absolute; top: 0px; left: 0px; }
.math { font-size: 1rem; }
.md-toc { min-height: 3.58rem; position: relative; font-size: 0.9rem; border-top-left-radius: 10px; border-top-right-radius: 10px; border-bottom-right-radius: 10px; border-bottom-left-radius: 10px; }
.md-toc-content { position: relative; margin-left: 0px; }
.md-toc::after, .md-toc-content::after { display: none; }
.md-toc-item { display: block; color: rgb(65, 131, 196); text-decoration: none; }
.md-toc-inner:hover { }
.md-toc-inner { display: inline-block; cursor: pointer; }
.md-toc-h1 .md-toc-inner { margin-left: 0px; font-weight: bold; }
.md-toc-h2 .md-toc-inner { margin-left: 2em; }
.md-toc-h3 .md-toc-inner { margin-left: 4em; }
.md-toc-h4 .md-toc-inner { margin-left: 6em; }
.md-toc-h5 .md-toc-inner { margin-left: 8em; }
.md-toc-h6 .md-toc-inner { margin-left: 10em; }
@media screen and (max-width: 48em) { 
  .md-toc-h3 .md-toc-inner { margin-left: 3.5em; }
  .md-toc-h4 .md-toc-inner { margin-left: 5em; }
  .md-toc-h5 .md-toc-inner { margin-left: 6.5em; }
  .md-toc-h6 .md-toc-inner { margin-left: 8em; }
}
a.md-toc-inner { font-size: inherit; font-style: inherit; font-weight: inherit; line-height: inherit; }
.footnote-line a:not(.reversefootnote) { color: inherit; }
.md-attr { display: none; }
.md-fn-count::after { content: '.'; }
.md-tag { opacity: 0.5; }
.md-comment { color: rgb(162, 127, 3); opacity: 0.8; font-family: monospace; }
code { text-align: left; }
h1 .md-tag, h2 .md-tag, h3 .md-tag, h4 .md-tag, h5 .md-tag, h6 .md-tag { font-weight: initial; opacity: 0.35; }
a.md-print-anchor { border: none !important; display: inline-block !important; position: absolute !important; width: 1px !important; right: 0px !important; outline: none !important; background-color: transparent !important; text-shadow: initial !important; background-position: initial initial !important; background-repeat: initial initial !important; }
.md-inline-math .MathJax_SVG .noError { display: none !important; }
.mathjax-block .MathJax_SVG_Display { text-align: center; margin: 1em 0em; position: relative; text-indent: 0px; max-width: none; max-height: none; min-height: 0px; min-width: 100%; width: auto; display: block !important; }
.MathJax_SVG_Display, .md-inline-math .MathJax_SVG_Display { width: auto; margin: inherit; display: inline-block !important; }
.MathJax_SVG .MJX-monospace { font-family: monospace; }
.MathJax_SVG .MJX-sans-serif { font-family: sans-serif; }
.MathJax_SVG { display: inline; font-style: normal; font-weight: normal; line-height: normal; zoom: 90%; text-indent: 0px; text-align: left; text-transform: none; letter-spacing: normal; word-spacing: normal; word-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; border: 0px; padding: 0px; margin: 0px; }
.MathJax_SVG * { transition: none; }


@include-when-export url(http://fonts.googleapis.com/css?family=Open+Sans:400italic,700italic,700,400&subset=latin,latin-ext);

/**
 * css forked from https://github.com/GitbookIO/gitbook 
 * www.gitbook.com
 * Apache License
 * https://github.com/GitbookIO/gitbook/blob/master/LICENSE
 **/

@font-face {
    font-family: 'Open Sans';
    font-style: normal;
    font-weight: normal;
    src: local('Open Sans Regular'),url('file:///Users/lx/Library/Application%20Support/abnerworks.Typora/themes/github/400.woff') format('woff')
}

@font-face {
    font-family: 'Open Sans';
    font-style: italic;
    font-weight: normal;
    src: local('Open Sans Italic'),url('file:///Users/lx/Library/Application%20Support/abnerworks.Typora/themes/github/400i.woff') format('woff')
}

@font-face {
    font-family: 'Open Sans';
    font-style: normal;
    font-weight: bold;
    src: local('Open Sans Bold'),url('file:///Users/lx/Library/Application%20Support/abnerworks.Typora/themes/github/700.woff') format('woff')
}

@font-face {
    font-family: 'Open Sans';
    font-style: italic;
    font-weight: bold;
    src: local('Open Sans Bold Italic'),url('file:///Users/lx/Library/Application%20Support/abnerworks.Typora/themes/github/700i.woff') format('woff')
}

html {
    font-size: 16px;
}

body {
    font-family: "Open Sans","Clear Sans","Helvetica Neue",Helvetica,Arial,sans-serif;
    color: rgb(51, 51, 51);
    line-height: 1.6;
}

#write{
    max-width: 860px;
  	margin: 0 auto;
  	padding: 20px 30px 40px 30px;
	padding-top: 20px;
    padding-bottom: 100px;
}
#write > ul:first-child,
#write > ol:first-child{
    margin-top: 30px;
}

body > *:first-child {
    margin-top: 0 !important;
}
body > *:last-child {
    margin-bottom: 0 !important;
}
a {
    color: #4183C4;
}
h1,
h2,
h3,
h4,
h5,
h6 {
    position: relative;
    margin-top: 1rem;
    margin-bottom: 1rem;
    font-weight: bold;
    line-height: 1.4;
    cursor: text;
}
h1:hover a.anchor,
h2:hover a.anchor,
h3:hover a.anchor,
h4:hover a.anchor,
h5:hover a.anchor,
h6:hover a.anchor {
    /*background: url("file:///Users/lx/Library/Application%20Support/images/modules/styleguide/para.png") no-repeat 10px center;*/
    text-decoration: none;
}
h1 tt,
h1 code {
    font-size: inherit;
}
h2 tt,
h2 code {
    font-size: inherit;
}
h3 tt,
h3 code {
    font-size: inherit;
}
h4 tt,
h4 code {
    font-size: inherit;
}
h5 tt,
h5 code {
    font-size: inherit;
}
h6 tt,
h6 code {
    font-size: inherit;
}
h1 {
    padding-bottom: .3em;
    font-size: 2.25em;
    line-height: 1.2;
    border-bottom: 1px solid #eee;
}
h2 {
   padding-bottom: .3em;
    font-size: 1.75em;
    line-height: 1.225;
    border-bottom: 1px solid #eee;
}
h3 {
    font-size: 1.5em;
    line-height: 1.43;
}
h4 {
    font-size: 1.25em;
}
h5 {
    font-size: 1em;
}
h6 {
   font-size: 1em;
    color: #777;
}
p,
blockquote,
ul,
ol,
dl,
table{
    margin: 0.8em 0;
}
li>ol,
li>ul {
    margin: 0 0;
}
hr {
    height: 4px;
    padding: 0;
    margin: 16px 0;
    background-color: #e7e7e7;
    border: 0 none;
    overflow: hidden;
    box-sizing: content-box;
    border-bottom: 1px solid #ddd;
}

body > h2:first-child {
    margin-top: 0;
    padding-top: 0;
}
body > h1:first-child {
    margin-top: 0;
    padding-top: 0;
}
body > h1:first-child + h2 {
    margin-top: 0;
    padding-top: 0;
}
body > h3:first-child,
body > h4:first-child,
body > h5:first-child,
body > h6:first-child {
    margin-top: 0;
    padding-top: 0;
}
a:first-child h1,
a:first-child h2,
a:first-child h3,
a:first-child h4,
a:first-child h5,
a:first-child h6 {
    margin-top: 0;
    padding-top: 0;
}
h1 p,
h2 p,
h3 p,
h4 p,
h5 p,
h6 p {
    margin-top: 0;
}
li p.first {
    display: inline-block;
}
ul,
ol {
    padding-left: 30px;
}
ul:first-child,
ol:first-child {
    margin-top: 0;
}
ul:last-child,
ol:last-child {
    margin-bottom: 0;
}
blockquote {
    border-left: 4px solid #dddddd;
    padding: 0 15px;
    color: #777777;
}
blockquote blockquote {
    padding-right: 0;
}
table {
    padding: 0;
    word-break: initial;
}
table tr {
    border-top: 1px solid #cccccc;
    background-color: white;
    margin: 0;
    padding: 0;
}
table tr:nth-child(2n) {
    background-color: #f8f8f8;
}
table tr th {
    font-weight: bold;
    border: 1px solid #cccccc;
    text-align: left;
    margin: 0;
    padding: 6px 13px;
}
table tr td {
    border: 1px solid #cccccc;
    text-align: left;
    margin: 0;
    padding: 6px 13px;
}
table tr th:first-child,
table tr td:first-child {
    margin-top: 0;
}
table tr th:last-child,
table tr td:last-child {
    margin-bottom: 0;
}

.CodeMirror-gutters {
    border-right: 1px solid #ddd;
}

.md-fences,
code,
tt {
    border: 1px solid #ddd;
    background-color: #f8f8f8;
    border-radius: 3px;
    padding: 0;
    font-family: Consolas, "Liberation Mono", Courier, monospace;
    padding: 2px 4px 0px 4px;
    font-size: 0.9em;
}

.md-fences {
    margin-bottom: 15px;
    margin-top: 15px;
    padding: 0.2em 1em;
    padding-top: 8px;
    padding-bottom: 6px;
}
.task-list{
	padding-left: 0;
}

.task-list-item {
	padding-left:32px;
}

.task-list-item input {
  top: 3px;
  left: 8px;
}

@media screen and (min-width: 914px) {
    /*body {
        width: 854px;
        margin: 0 auto;
    }*/
}
@media print {
    html {
        font-size: 13px;
    }
    table,
    pre {
        page-break-inside: avoid;
    }
    pre {
        word-wrap: break-word;
    }
}

.md-fences {
	background-color: #f8f8f8;
}
#write pre.md-meta-block {
	padding: 1rem;
    font-size: 85%;
    line-height: 1.45;
    background-color: #f7f7f7;
    border: 0;
    border-radius: 3px;
    color: #777777;
    margin-top: 0 !important;
}

.mathjax-block>.code-tooltip {
	bottom: .375rem;
}

#write>h3.md-focus:before{
	left: -1.5625rem;
	top: .375rem;
}
#write>h4.md-focus:before{
	left: -1.5625rem;
	top: .285714286rem;
}
#write>h5.md-focus:before{
	left: -1.5625rem;
	top: .285714286rem;
}
#write>h6.md-focus:before{
	left: -1.5625rem;
	top: .285714286rem;
}
.md-image>.md-meta {
    border: 1px solid #ddd;
    border-radius: 3px;
    font-family: Consolas, "Liberation Mono", Courier, monospace;
    padding: 2px 4px 0px 4px;
    font-size: 0.9em;
    color: inherit;
}

.md-tag{
	color: inherit;
}

.md-toc { 
    margin-top:20px;
    padding-bottom:20px;
}

#typora-quick-open {
    border: 1px solid #ddd;
    background-color: #f8f8f8;
}

#typora-quick-open-item {
    background-color: #FAFAFA;
    border-color: #FEFEFE #e5e5e5 #e5e5e5 #eee;
    border-style: solid;
    border-width: 1px;
}

#md-notification:before {
    top: 10px;
}

/** focus mode */
.on-focus-mode blockquote {
    border-left-color: rgba(85, 85, 85, 0.12);
}

header, .context-menu, .megamenu-content, footer{
    font-family: "Segoe UI", "Arial", sans-serif;
}


</style>
</head>
<body class='typora-export' >
<div  id='write'  class = 'is-mac'><h1><a name='header-c330' class='md-header-anchor '></a>SMRT测序在靶向捕获方面的更多应用</h1><div class='md-toc' mdtype='toc'><p class="md-toc-content"><span class="md-toc-item md-toc-h1" data-ref="c330"><a class="md-toc-inner" style="" href="#header-c330">SMRT测序在靶向捕获方面的更多应用</a></span><span class="md-toc-item md-toc-h2" data-ref="c335"><a class="md-toc-inner" style="" href="#header-c335">人HLA鉴定</a></span><span class="md-toc-item md-toc-h2" data-ref="c368"><a class="md-toc-inner" style="" href="#header-c368">BAC测序</a></span><span class="md-toc-item md-toc-h2" data-ref="c397"><a class="md-toc-inner" style="" href="#header-c397">解析含有高多态性免疫基因区域的复杂单倍型</a></span><span class="md-toc-item md-toc-h2" data-ref="c421"><a class="md-toc-inner" style="" href="#header-c421">参考文献</a></span></p></div><p><span id="hla"></span></p><h2><a name='header-c335' class='md-header-anchor '></a>人HLA鉴定</h2><ul><li>项目规模灵活（例如通过外显子2、3和/或4、或者整个HLA基因的相位进行调整）；</li><li>HLA基因SNP差异区域具有等位基因特异性的多态性；</li><li>实现无插补等位基因分离；</li><li>检测5’UTR，内含子和3’UTR内调节区的变异；</li><li>充分表征多克隆样品中的微小变异，如癌症或转录物；</li><li>无需参考基因组，可获得新的HLA等位基因的直接证据。</li></ul><p>表征蛋白质结合区域以外的HLA基因的多态性对于加强因果关联研究很重要[1]。高序列同源性和超多态性使确定真正的HLA等位基因多样性具有挑战性。二代测序仍存在二倍体模糊（DiploidAmbiguities）的问题，且依赖插补算法，尤其是当基因之间的同源序列长度超出大多数测序平台的能力时[2]。</p><p>利用单分子实时测序获得对免疫相关疾病因果关系，移植物抗宿主病在造血移植中的作用，药物超敏反应等的深入了解。</p><p>SMRT测序可以跨越大多数HLAI型和II型基因，可以直接获得HLA全长基因，无需插补[2]。</p><p><strong>特色研究：</strong>构建HLA II类基因的完整基因参考[3]</p><p><img src='http://www.pacb.com/wp-content/uploads/spotlight2-imputation-free-hla-typing.jpg' alt='' /></p><p>DKMS的免疫学家通过无需参考基因组的测序方法获得了HLA-DPB 1的完整基因。在研究时，IGMT/HLA数据库在550个已知的HLA-DPB 1等位基因中包含12个全长参考。在单次SMRT测序运行（一个Run）中，作者同时鉴定了48个样本，发现了9个新的等位基因。<a href='http://www.pacb.com/wp-content/uploads/ASHI_2015_DPB1.pdf'>了解更多</a></p><p><span id="bac"></span></p><h2><a name='header-c368' class='md-header-anchor '></a>BAC测序</h2><ul><li>在复杂区域内重建医学和发育重要的结构，如Y染色体；</li><li>将进化和农业研究的结构变异和单倍型信息精细地定位到感兴趣的基因；</li><li>达到铂金水平的基因组组装；</li><li>解决基因组研究（Draft Genome）中难以测序的历史遗留问题；</li><li>在单个SMRT Cell中进行数十个BAC的测序，使测序更加高效、经济。</li></ul><p>科学家通常使用细菌人工染色体（BacterialArtificial Chromosome，BAC）测序来弥补现有基因组组装中的缺口，或者作为靶向测序的方法来精细定位感兴趣的区域。那些具有GC-/AT-富集的BAC对二代测序来说是非常具有挑战性的。</p><p>利用SMRT测序，对成品BAC进行测序和组装可以达到高一致性和高精度，通常一个Contig可包含一个BAC。</p><p><strong>特色研究：</strong>解决玉米结构变异的BAC测序[4]</p><p><img src='http://www.pacb.com/wp-content/uploads/Spotlight-BAC-Targeted-Sequencing.jpg' alt='' /></p><p>基因组结构变异，包括拷贝数变异和插入/缺失变异，影响了大量的玉米遗传多样性。然而，其对表型的影响很大程度上仍未被探索。铝的毒性是酸性土壤作物生产的主要限制，占世界潜在耕地的50％。在这项研究中，科学家发现玉米铝耐受性与<em>MATE1</em>（multidrug and toxic compound extrusion 1）基因的三个拷贝相关。在重组近交系测绘群体中，AI抗性基因<em>MATE1</em>的拷贝数变异对表型变异的影响最大（数量性状），且与<em>MATE1</em>的表达量相关联。利用SMRT BAC测序对基因组的这个区域进行精细定位，使科学家们能够探索这种变异的进化基础，并开发改良的作物。</p><p><span id="mhc"></span></p><h2><a name='header-c397' class='md-header-anchor '></a>解析含有高多态性免疫基因区域的复杂单倍型</h2><ul><li>同时鉴定复杂免疫区域的基因型和单倍型而无需家系研究；</li><li>在具有扩展的连锁不平衡的复杂区域（疾病相关或群体研究中）发现相关变异；</li><li>在使用较小样本量时增加您疾病相关研究的统计学意义；</li><li>在复杂的KIR基因区域检测基因顺序、CNV或鉴定基因型。</li></ul><p>包括HLA基因和Killer免疫受体（Killer
Immune Receptor，KIR）基因簇的主要组织相容性复合物（MHC）代表了与各种疾病状况相关的一些关键的免疫单倍型，包括自身免疫，病毒感染，生殖失败，移植物抗宿主 疾病和癌症。科学家们继续探索这些疾病的基本机制和免疫系统的演变。然而，这些基因组区域中的巨大连锁不平衡，高基因密度，拷贝数变异，高度复杂重复和极端多态性使得这些单倍型难以表征[5]。</p><p><strong>特色研究：</strong>在与I型糖尿病相关的扩展的免疫基因组区域获得完整的分阶段基因组序列[6]</p><p><img src='http://www.pacb.com/wp-content/uploads/Spotlight-Total-DR4-Align-with-SSTO.jpg' alt='' /></p><p>美国华盛顿大学弗雷德哈钦森（Fred Hutchinson）癌症研究中心的科学家开发了一种利用Fosmid测序和长读长SMRT测序以产生MHC和KIR2扩展的基因组亚区域的完整的，能够分辨单倍型的序列的方法。他们发现I型糖尿病个体特有的新序列区。他们现在已经建立了更经济的方法来更全面地识别与免疫疾病相关的变异。<a href='http://www.pacb.com/wp-content/uploads/AGBT-2015-Poster-Dan-Geraghty.pdf'>了解更多</a></p><h2><a name='header-c421' class='md-header-anchor '></a>参考文献</h2><p>[1] Hosomichi, K., et al., (2015) <a href='http://www.nature.com/jhg/journal/v60/n11/full/jhg2015102a.html'>The impact of next-generation sequencing technologies on HLA research</a>. <em>Journal of Human Genetics.</em> 60 (11), 665–673.</p><p>[2] Nelson, W. C., et al., (2015) <a href='http://www.sciencedirect.com/science/article/pii/S019888591500155X'>An integrated genotyping approach for HLA and other complex genetic systems</a>. <em>Human Immunology</em>. 76 (12), (928-938).</p><p>[3] Lang, K. et al. (September, 2015) <a href='http://www.pacb.com/wp-content/uploads/ASHI_2015_DPB1.pdf'>Phased full-length SMRT Sequencing of HLA DPB1</a>. <em>Poster presented at 41st Annual Meeting of the American Society for Histocompatibility and Immunogenetics.</em> Savannah, GA..</p><p>[4] Maron, L.G. et al. (2013) <a href='http://www.pnas.org/content/110/13/5241.full'>Aluminum tolerance in maize is associated with higher MATE1 gene copy number</a>. <em>Proceedings of the National Academy of Sciences.</em> 110(13), 5241-5246.</p><p>[5] Trowsdale, J., and Knight, J., (2013) <a href='http://www.annualreviews.org/doi/abs/10.1146/annurev-genom-091212-153455'>Major histocompatibility complex genomics and human disease</a>. <em>Annual Review Genomics and Human Genetics</em>. 14, 301-323.</p><p>[6] Geraghty, D., et al. (February, 2015) <a href='http://www.pacb.com/wp-content/uploads/AGBT-2015-Poster-Dan-Geraghty.pdf'>Complete resequencing of extended genomic regions using fosmid target capture and Single Molecule Real-Time (SMRT) long read sequencing technology</a>. <em>Poster presented at Advances in Genome Biology &amp; Technology Conference</em>. Marco Island, FL.</p></div>
</body>
</html>